Today, type-II diabetics are continuously increasing in Japan, and the estimated number of the same exceeds 8,200,000. As a measure against this increase, interventions for preventing diabetes from developing have been made based on the glucose tolerance test, resulting, however, in unsatisfactory effects. The cause is as follows: at such a borderline stage that functional abnormalities are found by the glucose tolerance test, disorders of pancreatic islets have already advanced to a high degree, and this stage possibly is too late as a time for starting interventions.
More specifically, in the diabetes developing process, the amount of pancreatic islets (particularly, the amount of pancreatic β-cells) decreases prior to the occurrence of glucose tolerance abnormalities. Therefore, when functional abnormalities are detected or there are subjective symptoms, diabetes has already reached the stage where it is too difficult to be treated. On the other hand, if a decrease in the amount of pancreatic islets and/or the amount of pancreatic β-cells can be detected at an early stage, there is a possibility for the prevention and treatment of diabetes. Therefore, a noninvasive technique for imaging pancreatic islets, particularly a noninvasive technique for imaging pancreatic islets for determining the amount of the pancreatic islets and/or the amount of pancreatic β-cells, has been desired for the prevention and diagnosis of diabetes. Among the noninvasive techniques, a molecular probe that enables imaging of pancreatic islets, preferably pancreatic β-cell, and noninvasive determination of an amount of pancreatic β-cells has been desired in particular.
In designing a molecular probe for imaging of pancreatic islets, various target molecules in pancreatic islet cells, particularly functional proteins specific for the β-cells, are being researched. Among these molecular probes, GLP-1R (glucagon-like peptide-1 receptor) is being researched as a target molecule; GLP-1R is distributed in pancreatic β-cells, and is a seven-transmembrane G protein coupled receptor.
As a molecular probe for pancreatic β-cells imaging that uses GLP-1R as a target molecule, a molecular probe obtained by labeling a derivative of exendin-4(9-39) as a GLP-1R antagonist with [18F] fluorine has been researched (e.g., H. Kimura et al. Development of in vivo imaging agents targeting glucagons-like peptide-1 receptor (GLP-1R) in pancreatic islets. 2009 SNM Annual Meeting, abstract, Oral Presentations No. 326 (Document 1)).
Further, a molecular probe for imaging a GLP-1R-positive tumor has been researched as an imaging probe targeting GLP-1R as a target molecule. Examples of the molecular probe for imaging a GLP-1R-positive tumor include a molecular probe obtained by labeling a derivative of exendin-4 as an GLP-1R agonist with [min] indium via diethylenetriaminepentaacetic acid (DTPA); and a molecular probe obtained by labeling a derivative of exendin-4(9-39) as a GLP-1R antagonist with [111-In] indium via DTPA (e.g., M. Beche et al. Are radiolabeled GLP-1 receptor antagonists useful for scintigraphy? 2009 SNM Annual Meeting, abstract, Oral Presentations No. 327 (Document 2)).
However, another molecular probe for imaging of pancreatic islets is ultimately preferred to enable noninvasive three-dimensional imaging of pancreatic islets.